Drug Combination to Treat Melanoma

Abstract

This invention relates to the combination of vemurafenib and the heat shock protein 90 (HSP90) inhibitor XL888 to treat melanoma, particularly BRAF V600 mutant melanoma in patients in need of such treatment.

1 . A method of treating BRAF V600 mutant melanoma comprising administering to a patient in need of such treatment a combination comprising vemurafenib in combination with the heat shock protein90 (HSP90) inhibitor XL888 or a pharmaceutically acceptable salt thereof, wherein vemurafenib is dosed orally at up to 960 mg twice daily and XL888 is dosed orally at up 90 mg twice a week. 
     
     
         2 . The method of  claim 1 , wherein vemurafenib is dosed orally at 480 mg twice daily. 
     
     
         3 . The method of  claim 1 , wherein vemurafenib is dosed orally at 720 mg twice daily. 
     
     
         4 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 120 mg twice weekly. 
     
     
         5 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 105 mg twice weekly. 
     
     
         6 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 90 mg twice weekly. 
     
     
         7 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 75 mg twice weekly. 
     
     
         8 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 60 mg twice weekly. 
     
     
         9 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 45 mg twice weekly. 
     
     
         10 . The method of  claims 1 - 3 , wherein XL888 is dosed orally at 30 mg twice weekly. 
     
     
         11 . The method of  claims 1 - 10 , wherein vemurafenib and XL888 are each present in a separate pharmaceutically acceptable composition and the compositions are administered simultaneously. 
     
     
         12 . The method of  claims 1 - 10 , wherein vemurafenib and XL888 are each present in a separate pharmaceutically acceptable composition and the compositions are administered sequentially. 
     
     
         13 . A method of treating melanoma in a human patient comprising administering an effective amount of a combination of vemurafenib and XL888 or a pharmaceutically acceptable salt thereof to the patient, wherein the combination of vemurafenib and XL888 has greater anticancer activity against said melanoma in the human patient than the maximum tolerated dose of vemurafenib against said melanoma in the human patient or the maximum tolerated dose of XL888 alone against said melanoma in the human patient. 
     
     
         14 . The method of  claim 1 , wherein the combination of vemurafenib and XL888 has greater anticancer activity against said melanoma in the human patient than the optimum dose of each drug alone against said melanoma in the human patient.